A new study by the U.S. National Institutes of Health (NIH) has confirmed that resistance is growing to one of the key drugs being used to fight malaria in Cambodia, a situation likely to worsen and which could lead to a growing caseload in the coming years.

Health workers first detected the mosquito-borne parasite’s resistance to artemisinin in the artemisinin-based combination therapies being used as the front-line defense against malaria in 2007 along the Thai-Cambodian border, the first sign of its pending failure anywhere in the world.
The new study by the NIH’s National Institute of Allergy and Infectious Diseases, published last week by The Lancet, confirms resistance to piperaquine, another key drug that has been used in the combination therapies.
“Resistance to artemisinin in parts of Southeast Asia is well documented, but until now only a few studies have presented clear evidence of piperaquine resistance,” the NIH said in a statement on the study.
The researchers studied the presence of the deadliest strain of malaria, Plasmodium falciparum, in 204 infected patients aged 2 to 65 after they took a standard treatment of dihydroartemisinin and piperaquine in the provinces of Ratanakkiri, Preah Vihear and Pursat over 63 days.
In the last two provinces, where the combination performed most poorly, the NIH said laboratory tests showed “that both artemisinin and piperaquine resistance contributed to treatment failure.”

In combination therapies such as the one studied, the artemisinin is meant to deliver the initial blow against malaria, wiping out the majority of the parasites, while the partner drug then sweeps up what is left.
The loss of both drugs in western Cambodia is a serious setback to the country’s fight against the disease, said Didier Menard, who heads the malaria unit at the Pasteur Institute in Phnom Penh.
Mr. Menard said health workers first noticed resistance to this particular combination in 2011 in Pailin province, initially to artemisinin.
“Now we have resistance to the partner drug, which is piperaquine,” he said. “It is bad news because…we don’t have a really good new treatment.”
Mr. Menard points out that the combination is not yet failing to cure malaria-infected patients altogether.
But it is taking more and more time to work, which indicates that it is getting weaker.
He said the trend is likely only to get worse.
While growing resistance to piperaquine is unlikely to cause a spike in fatal malaria cases, the overall number of malaria cases “is likely to increase,” he said.

Total figures on malaria cases in 2015 are not yet available. But according to the government’s National Malaria Center, Cambodia saw 41,000 malaria cases over the first nine months of last year, up from 25,000 cases over the same period the year before.
The latest study is not all bad news, however.
The researchers found that the same parasites resisting piperaquine showed increased susceptibility to another partner drug—mefloquine. They say a combination of artemisinin and mefloquine might be a better first-line combination in areas of Cambodia where artemisinin and piperaquine are failing.
Mr. Menard said the government came to the same conclusion back in 2014 and made a combination drug with mefloquine the first-line treatment in Battambang, Oddar Meanchey, Pailin and Pursat.“But it’s only on paper,” he added, noting that an initial lack of interest by an Indian supplier to fill an order as small as Cambodia’s had delayed delivery.
Mr. Menard said he was not sure if the prescribed mefloquine-based drugs had since arrived. The National Malaria Center could not be reached for comment.
But even mefloquine will be only a temporary solution for Cambodia. Malaria has developed resistance to the drug in parts of Cambodia before, and Mr. Menard said that—if reintroduced—it would be a few years at best before it happened again.